BioSimilars vs. Generic Drugs: What’s In a Word?

“Biosimilars” is a buzzword that isn’t going away anytime soon. Sometimes also referred to as “follow-on biologics”, biosimilar is the term used for a biologic drug that is produced using a different cell line, master cell bank, and/or different process than the one that originally produced the product.
How do biosimilars differ from so-called generic drugs? Generic drugs are essentially “copycat” versions of small molecule drugs – drugs that can be synthesized in the lab by following standardized, pre-defined procedures. Using well-established analytic techniques, the generic version of a small molecule drug can be demonstrated to be chemically and structurally identical to the innovator drug.

Biologic drugs, however, are much more complex than small molecule drugs. These drugs are proteins that must be produced by a living cell – they cannot be chemically synthesized in the lab by following a standard set of procedures. The cell makes these proteins by following a recipe provided by a short sequence of DNA – a gene – that is inserted into the cell. Here’s the catch: even if two different cells are provided the exact same recipe, the final product may be slightly different. This may happen even if the two cells are of the same type – very slight environmental differences can have a profound effect on how a given cell follows a particular recipe. This makes intuitive sense – we know that we can follow the same recipe that the gourmet chef at our favorite restaurant follows, but somehow, the dish doesn’t taste quite as good. Slight difference such as the exact temperature of the frying pan, the brand of the heavy cream, and even the humidity level and elevation of the kitchen will influence the final outcome. The restaurant industry depends on these “trade secrets” to keep us coming back for more.

Complicating matters further for biosimilar products is the fact that because biologic drugs are structurally much more complex than their small molecule counterparts, it is not currently possible to demonstrate conclusively that a biosimilar drug is in fact identical to the original biologic drug. Thus, since we know that there is a high likelihood that a biosimilar drug is not identical to the original biologic, and we have no way of precisely measuring whatever differences may exist, the term “biosimilar” is used rather than “generic”, which implies identity.

What implications does all of this have for regulation and marketing approval? Next week’s blog will discuss the similarities and differences in how various regions of the world have approached this issue.